Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• poorly soluble hydroxyamino acids efficiently, 4) it should preferably be fully miscible with a wide range of acyl halides and carboxylic anhydrides (including long-chained fatty-acid derived ones) and if possible, 5) the acid constituent(s) should have only a moderate affinity for amines such that

Electrochemical oxidation of cholesterol

• Jacek W. Morzycki and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2015, 11, 392–402, doi:10.3762/bjoc.11.45

• oxidation current. However, cholesterol in blood is mainly present in form of its fatty acid esters. If the total cholesterol amount is needed, the cholesterol esters must be hydrolyzed prior to analysis by the use of cholesterol esterase [51]. A poor stability of the enzymes and an influence of various

Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers

• Thorbjørn Terndrup Nielsen,
• Catherine Amiel,
• Laurent Duroux,
• Kim Lambertsen Larsen,
• Lars Wagner Städe,
• Reinhard Wimmer and
• Véronique Wintgens

Beilstein J. Org. Chem. 2015, 11, 147–154, doi:10.3762/bjoc.11.14

• of nanoparticles. It has been shown that CD polymers can form nanoparticles when associated with various amphiphilic polymers such as dextran modified with fatty acid chains [15] or adamantane [16] in aqueous solution. Simply by mixing solutions of β-CD polymers and the hydrophobic-modified dextrans

Effects of RAMEA-complexed polyunsaturated fatty acids on the response of human dendritic cells to inflammatory signals

• Éva Rajnavölgyi,
• Renáta Laczik,
• Viktor Kun,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3152–3160, doi:10.3762/bjoc.10.332

• lipopolysaccharide and polyinosinic:polycytidylic acid, mimicking bacterial and viral infections, respectively. The response of unstimulated and activated moDC to n−3 fatty acid treatment was tested by measuring the cell surface expression of CD1a used as a phenotypic and CD83 as an activation marker of inflammatory

• diseases [7]. Intake of dietary fats may influence inflammation in the gastrointestinal tract. In a long-term study conducted on 170 805 women a reduced risk of ulcerative colitis was observed for the participants with high intake of n−3 PUFAs [8]. The fatty acid composition of the diet, in particular, the

• proportion of different types of PUFAs, has an influence on the fatty acid composition of immune cells which is a chemical trigger for immune response, such as inflammation [9]. Supplementation of the diet of healthy human volunteers with n−3 PUFAs was unambiguously beneficial: the number of monocytes and

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• rate and enantioselectivity of the enzymatic reactions could be significantly improved by using fatty acid vinyl esters. After analyzing the effect of those acyl group donors general findings can be presented: (i) (S)-(+)-5 alcohol with excellent enantiomeric excess (>99% ee) could be obtained after a

• relatively high volatility (hence possibility of easy recovery of the product and remaining substrate), and (ii) lower cost when compared to the employed long-chain fatty acid vinyl esters, as well as the fact that (iii) vinyl acetate displayed acceptable impact on the performance of the lipases, we reasoned

A study on the inhibitory mechanism for cholesterol absorption by α-cyclodextrin administration

• Takahiro Furune,
• Naoko Ikuta,
• Yoshiyuki Ishida,
• Hinako Okamoto,
• Daisuke Nakata,
• Keiji Terao and
• Norihiro Sakamoto

Beilstein J. Org. Chem. 2014, 10, 2827–2835, doi:10.3762/bjoc.10.300

• . reported that one mol of C16–C18 fatty acid was complexed with three mol of α-CD [2], it is possible that (1-palmitoyl-2-oleoyl)lecithin, a major component of lecithin [32], was complexed with up to six α-CD molecules. These results suggest that the two fatty acids of lecithin were complexed with four or

• results of Minekus et al. [36]. RM did not decrease micellar cholesterol solubility in FeSSIF. It has been reported that RM decreases postprandial triglyceride elevation, and it was suggested that the mechanism was the stabilization of mixed micelles of fatty acids, fatty acid esters and bile salts [37

• has beneficial effects on body weight control, lipid metabolism, glucose metabolism, prebiotics, allergy suppression and other functions [9][10][11][12][13][14][15][16][17]. It is thought that the mechanism behind the lowering of blood triglycerides by α-CD was the latter’s complexation with the fatty

A green approach to the synthesis of novel phytosphingolipidyl β-cyclodextrin designed to interact with membranes

• Yong Miao,
• Florence Djedaïni-Pilard and
• Véronique Bonnet

Beilstein J. Org. Chem. 2014, 10, 2654–2657, doi:10.3762/bjoc.10.278

• using a green methodology. Reactions using greener and safer catalysts with more environmentally friendly purification solvents were performed. Four unreported mono-substituted cyclodextrins bearing a phytosphingolipidyl chain and a fatty acid chain (C10, C12, C14 and C18) were successfully obtained

• (yield = 80%, see Scheme 1). Indeed, COMU is an efficient peptide coupling reagent and can be used in the synthesis of cyclodextrin derivatives. Insertion of fatty acid chain In previous work, the synthesis of the reaction of permethylated 6-amino-6-deoxy-β-cyclodextrin and vinyl ester catalyzed by

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

• Michail Syrpas,
• Ewout Ruysbergh,
• Christian V. Stevens,
• Norbert De Kimpe and
• Sven Mangelinckx

Beilstein J. Org. Chem. 2014, 10, 2539–2549, doi:10.3762/bjoc.10.265

• atoms, that could be involved in such interactions seem an interesting strategy to be explored. Surprisingly, most of the studies focus on altering the fatty acid tail or the lactone ring of the AHL molecules [14][19], while modifications at the α-carbon position with respect to the carbonyl function of

• conditions were used for the preparation of AHLs with unfunctionalized acyl chains in a convenient way. The brominated fatty acids 5, except the commercially available α-bromohexanoic acid (5a), were prepared by a Hell–Volhard–Zelinsky bromination of the corresponding fatty acid 4 with molecular bromine and

• appropriate α-bromo fatty acid 5 with (S)-homoserine lactone 1 (Scheme 2). For α-iodo fatty acids 7, two different routes were evaluated. Iodinated fatty acids 7e,f were prepared via reaction of the corresponding fatty acids 4e,f with iodine and chlorosulfonic acid [28]. However, this transformation was not

Sacrolide A, a new antimicrobial and cytotoxic oxylipin macrolide from the edible cyanobacterium Aphanothece sacrum

• Naoya Oku,
• Miyako Matsumoto,
• Kohsuke Yonejima,
• Keijiroh Tansei and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2014, 10, 1808–1816, doi:10.3762/bjoc.10.190

• isolation of an unusual ω-1 fatty acid (9Z,12Z)-9,12,15-hexadecatrienoic acid from a freshwater periphytic cyanobacterium Nostoc verrucosum [4]. Aphanothece sacrum is also an edible cyanobacterium, which is an endemic species in the Aso water system in the Kyushu District, Japan. It inhabits oligotrophic

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• compounds with bouquets composed of up to 100 different compounds [1][2][3][4][5][6]. Major volatile classes comprise aliphatic compounds derived from fatty acid metabolism, terpenes, aromatic compounds, sulfur compounds, and pyrazines [1]. Apart from pyrazines, indole, and a few strain specific compounds

Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• (15%). To assess whether the concept of regioselectivity hotspots near the heme was transferable, residues that are equivalent to the two hotspot positions in CYP102A1 were mutated in CYP153A from Marinobacter aquaeolei. In the fatty acid ω-hydroxylase CYP153A, L354 corresponds to A328 in CYP102A1

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• a cooperative effect [94], which means that albumin binding significantly increases until an appropriate fatty acid chain length is reached. In 1998, seven binding sites of this multifunctional transport protein were identified by Curry et al. using X-ray crystallographic studies [95]. Later on

• modified by fatty acid acylation [97]. The synthesis of these lipidated peptides can be performed by amidation, S- or O-esterification as well as thioether or -sulfide formation. Owing to the strength of the covalent bonds, amidation and O-esterfication are preferred over the other strategies [97

• enables specific amide-bond formation by the reaction of an activated carboxylic group of the fatty acid with the Nε-group of the lysine. The introduction of a glutamyl spacer can be helpful in order to increase the solubility of the drug candidates [99][106]. Lipidation of peptide hormones has led to

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• ], as monosulfuric acid ester [6] or as potential acylation site for fatty acid side chains such as in A- and B-series muraymycin nucleoside antibiotics (Figure 1) [7][8][9]. In the case of these muraymycin congeners, acylation of the 3-hydroxy position with fatty acid side chains, which are ω

• active site located on the cytosolic side of the membrane [10][11][12][13][14]. For previously reported SAR studies on muraymycins and their analogues, the fatty acid side chain was either neglegted or replaced with a structurally distinct lipophilic mimic [15][16][17]. Mansour and co-workers found a

• moiety to the muraymycin scaffold. As part of our synthetic studies on muraymycins and their analogues [19][20][21][22][23][24], including investigations on the unusual ω-functionalized fatty acid motif found in muraymycin A1 (1a) [25], we identified the need for a highly stereoselective synthesis of (2S

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• ], the CB1 receptor of cannabinoid and fatty acid amide hydrolase [114][118][119][120][121]. In this context, Hulme and co-workers described a Passerini multicomponent approach towards cis-constrained norstatine mimics, a class of HIV-1 protease inhibitors with a tetrazole core (Scheme 45) [122]. They

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• cyclohepta[cd]oxindole core 32 proved the synthetic versatility of a [3,3]-sigmatropic rearrangement for direct C–C-bond formation at the C4 position of the indole nucleus, and thus provides experimental evidence for the biosynthetic proposal. Applications to natural product synthesis Fatty acid metabolites

• divinylcyclopropane–cycloheptadiene rearrangement has been developed as a versatile method for the construction of seven-membered rings. The utilization in the total synthesis of both sesqui- and diterpenoid natural products as well as in the total synthesis of alkaloids and fatty acid-derived metabolites underlines

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• intermediate, putatively phloroglucinol (12) [36]. Nitrophenol 13 likely constitutes a direct biosynthetic precursor of the myxocoumarins. Upon O-acetylation of 13 with the long-chain β-keto acid building block 14, putatively recruited from fatty-acid biosynthesis, the intermediate ester 15 could undergo C–C

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• by fatty acid synthases to the final iso-fatty acids (even numbered for isobutyryl-CoA; odd-numbered for isovaleryl-CoA) through extension with malonyl-CoA [21][22]. Long-chain iso-fatty acids are important analytical reference compounds owing to the presence of these materials in tobacco [23], wool

• ), from readily available starting materials. To illustrate the opportunities that our approach provides, we demonstrate the elaboration of the C17-iso-fatty acid 6 and an intermediate, 22, to several terminal-branched natural products that have not previously been synthesized. Results and Discussion Our

Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis

• Stephan Klopries,
• Uschi Sundermann and
• Frank Schulz

Beilstein J. Org. Chem. 2013, 9, 664–674, doi:10.3762/bjoc.9.75

• widespread application in current medicine and agriculture. Polyketide synthases (PKS), giant multienzyme complexes, play a pivotal role in their biosynthesis. PKS generate molecular complexity and diversity through a number of stepwise condensations in analogy to fatty acid synthases but with optional and

A peptidic hydrogel that may behave as a “Trojan Horse”

• Nicola Castellucci,
• Giorgio Sartor,
• Natalia Calonghi,
• Carola Parolin,
• Giuseppe Falini and
• Claudia Tomasini

Beilstein J. Org. Chem. 2013, 9, 417–424, doi:10.3762/bjoc.9.44

• the xerogel, making a complex network. The gelator is derived from α-amino acids (Thr, Phe) and a fatty acid (azelaic acid) and is biocompatible: it was dosed to IGROV-1 cells, which internalized it, without significantly affecting the cell proliferation. To check the internalization process by

• carry drug molecules into the cell. For this purpose, we used the gelator A (Figure 1), derived from natural proteinogenic amino acids (Thr, Phe) and a fatty acid (azelaic acid). Compound A was prepared from Boc-L-Phe-D-Oxd-OBn and azelaic acid, as previously reported [23]. To check the cellular uptake

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• studying the kinetics of phalloidin-induced disturbances in the actin system of a cell in correlation with, for example, the development of apoptosis in the cell. Experimental Fatty acid esters of phalloidin Ten micromoles of phalloidin was dissolved in 0.1 mL dry pyridine and reacted with 0.3 µmol of

• . After evaporation in vacuo at 60 °C, the aminophalloidin was purified on a Sephadex-LH20 column with methanol as eluant. Yield of aminophalloidin was 80%, purity 89% by HPLC. Fatty acid amides of phalloidin Aminophalloidin and the fatty acid chlorides were reacted as described for the synthesis of

Identification and isolation of insecticidal oxazoles from Pseudomonas spp.

• Florian Grundmann,
• Veronika Dill,
• Andrea Dowling,
• Aunchalee Thanwisai,
• Edna Bode,
• Narisara Chantratita,
• Richard ffrench-Constant and
• Helge B. Bode

Beilstein J. Org. Chem. 2012, 8, 749–752, doi:10.3762/bjoc.8.85

• side chains was concluded from a fatty-acid analysis of the producing strain, which showed only straight-chain fatty acids (data not shown). In order to confirm the structure of all oxazole derivatives, to compare their retention times, and to provide enough material for bioactivity tests, oxazoles 3–6

Synthesis and antifungal properties of papulacandin derivatives

• Marjolein van der Kaaden,
• Eefjan Breukink and
• Roland J. Pieters

Beilstein J. Org. Chem. 2012, 8, 732–737, doi:10.3762/bjoc.8.82

• -1042 [25], corynecandin [26][27] and the F-10748 series [28]. These structures vary mostly with respect to the two partially unsaturated acyl chains on the sugars. Small changes in these fatty acid tails have only small effects on the activity. However, more drastic changes in these tails or the lack

• hydroxy groups were reprotected with MOM groups by using MOM-Cl to give 36. Then the glucose O(3) needed to be selectively deprotected for the incorporation of the fatty acid tail. Unfortunately, this was not possible from 36 because of the use of the more stable TIPS group in this synthesis. Therefore

The volatiles of pathogenic and nonpathogenic mycobacteria and related bacteria

• Thorben Nawrath,
• Georgies F. Mgode,
• Bart Weetjens,
• Stefan H. E. Kaufmann and
• Stefan Schulz

Beilstein J. Org. Chem. 2012, 8, 290–299, doi:10.3762/bjoc.8.31

• fatty-acid derivatives were released by pathogenic/nonpathogenic mycobacteria, while the two Nocardia spp. (N. asteroides and N. africana) emitted the sesquiterpene aciphyllene. Pathogenic Mycobacterium tuberculosis strains grown on agar plates produced a distinct bouquet with different volatiles, while

• compounds are listed in Table 1. In addition to previously reported compounds 1–4 [9], several new volatiles were identified, predominantly aromatic compounds, such as 4-methylanisole (5), methyl salicylate (6), methyl 2-aminobenzoate (7), and methyl and ethyl benzoate (8 and 9), as well as fatty-acid

• previously observed volatiles 1, 5, 7, and 8, as well as the fatty acid derivative 10, were present in the headspace extracts. Frequently, mycobacteria are observed to grow faster in liquid medium than on solid medium [31][32]. Consistent with this, M. tuberculosis strain 5 produced the most volatiles after

Conserved and species-specific oxylipin pathways in the wound-activated chemical defense of the noninvasive red alga Gracilaria chilensis and the invasive Gracilaria vermiculophylla

• Martin Rempt,
• Florian Weinberger,
• Katharina Grosser and
• Georg Pohnert

Beilstein J. Org. Chem. 2012, 8, 283–289, doi:10.3762/bjoc.8.30

• chemical defense against epiphytism has been demonstrated. This alga has two major lines of defense, including a rapid wound-activated production of oxylipins and a slower induced defense involving the up regulation of phospholipases and lipoxygenases and subsequent fatty-acid transformation [3][5]. Among

• demonstrate that the structurally diverse oxylipins detected in Gracilaria spp. play individual roles in the chemical defense against different herbivores. The dihydroxylated fatty acid 7,8-di-HETE is generally active against co-evolved herbivores, while prostaglandins support an invasive success of the algae

• same procedure was followed in the absence of the labeled fatty acid. Quantitative analysis. The extracted or commercially available compounds were used to create three calibration standards for each analyte, covering the concentration range detected in the extract from wounded algae. A calibration

Novel fatty acid methyl esters from the actinomycete Micromonospora aurantiaca

• Jeroen S. Dickschat,
• Hilke Bruns and
• Ramona Riclea

Beilstein J. Org. Chem. 2011, 7, 1697–1712, doi:10.3762/bjoc.7.200

• (CLSA) and analysed by GC–MS. The headspace extracts contained more than 90 compounds from different classes. Fatty acid methyl esters (FAMEs) comprised the major compound class including saturated unbranched, monomethyl and dimethyl branched FAMEs in diverse structural variants: Unbranched, α-branched

• with isotopically labelled [2H10]leucine, [2H10]isoleucine, [2H8]valine, [2H5]sodium propionate, and [methyl-2H3]methionine demonstrated that the responsible fatty acid synthase (FAS) can use different branched and unbranched starter units and is able to incorporate methylmalonyl-CoA elongation units

• for internal methyl branches in various chain positions, while the methyl ester function is derived from S-adenosyl methionine (SAM). Keywords: actinomycetes; FAMEs; fatty acid biosynthesis; GC–MS; volatiles; Introduction Lipids in general, and particularly fatty acids (FAs), belong to the most